Search

The marine sponge Acanthodendrilla sp. contains the proteasome inhibitor acanthosulfate ( 4), a disulfated merosesterterpene having a scalarane-type skeleton. The structure of acanthosulfate ( 4), which possesses an unusual configuration, was elucidated by interpretation of spectroscopic data.

Sponges are host to extremely diverse bacterial communities, some of which appear to be spatiotemporally stable, though how these consistent associations are assembled and maintained from one sponge generation to the next is not well understood. Here we report that a diverse group of microbes, including both bacteria and archaea, is consistently present in aggregates within embryos of the tropical sponge Corticium sp. The major taxonomic groups represented in bacterial 16S rRNA sequences amplified from the embryos are similar to those previously described in a variety of marine sponges. Three selected bacterial taxa, representing proteobacteria, actinobacteria, and a clade including recently described sponge-associated bacteria, were tested and found to be present in all adult samples tested over a 3-year period and in the embryos throughout development. Specific probes were used in fluorescence in situ hybridization to localize cells of the three types in the embryos and mesohyl. This study confirms the vertical transmission of multiple, phylogenetically diverse microorganisms in a marine sponge, and our findings lay the foundation for future work on exploring vertical transmission of specific, yet diverse, microbial assemblages in marine sponges.

Three new hexaprenoid hydroquinones, adociaquinol (1), adociasulfate 11 (2), and adociasulfate 12 (3), together with the known adociasulfates 2, 4, and 6, were isolated from the marine sponge Haliclona (aka Adocia) sp. The structures of these compounds were elucidated by interpretation of spectroscopic data.

Certain species of marine sponges in the order Dictyoceratida harbor large populations of the cyanobacterial symbiont Oscillatoria spongeliae in the mesohyl (interior) of the sponge. We show that in four of these sponge species (Lamellodysidea herbacea, Lamellodysidea chlorea, Lendenfeldia chondrodes, and Phyllospongia papyracea) from Palau there is a consistent community of alpha-proteobacteria in addition to O. spongeliae that fall within the Rhodobacter group based on 16S rRNA gene analysis. Some of the alpha-proteobacteria in Lendenfeldia chondrodes and P. papyracea but not in the Lamellodysidea spp. contained site-specific insertions in the 16S rRNA gene. Reverse transcription-PCR experiments demonstrated that the largest insertion found in this study (63 bp) is present in the mature rRNA. Lendenfeldia chondrodes was the only sponge found to have another cyanobacterium in the tissue, a Synechocystis sp. We found that the Synechocystis sp. was present in both the pinacoderm (surface epithelial tissue) and mesohyl, in contrast to O. spongeliae, which was only found in the mesohyl through the use of specific fluorescence in situ hybridization experiments. Of the four sponge species, only P. papyracea was found to contain a significant number of gamma-proteobacteria. These results demonstrate that O. spongeliae-dominated bacterial communities in different sponge species can vary considerably and increase our understanding of the bacterial communities found in marine invertebrates.

The isolation from the marine sponge Leiosella cf. arenifibrosa and structural elucidation of halipeptin D (5), a relative of the previously isolated halipeptins A-C (1-3), is described along with the total synthesis of a number of oxazoline analogues (7 a-d and epi-7 c-d). The developed synthetic strategy provides a flexible entry into the various isomers of the polyketide domain of the halipeptins and improvises for a late stage construction of the oxazoline ring after a macrolactamization process which secures the required macrocycle.

The lithistid sponge Scleritoderma nodosum contains a new cyclic peptide, scleritodermin A (1), the structure of which incorporates l-proline, l-serine, and keto-allo-isoleucine units as well as a novel conjugated thiazole moiety (ACT) and O-methyl-N-sulfoserine. Scleritodermin A (1) inhibited tubulin polymerization and showed significant in vitro cytotoxicity against human tumor cell lines.

Four new steroidal alkaloids, plakinamine I-K (1-3) and dihydroplakinamine K (4), were isolated from the marine sponge Corticium niger. The structures of these compounds were elucidated by interpretation of spectroscopic data. Compounds 1-4 exhibit significant in vitro cytotoxicity.

Five novel brominated polyacetylenic diols, diplynes A-E (2-6), and three sulfated analogues, diplyne A 1-sulfate (7), diplyne C 1-sulfate (8), and 2-deoxydiplyne D sulfate (9), were isolated from the Philippines sponge Diplastrella sp. by employing bioassay-guided fractionation using the HIV-1 integrase inhibition assay. The novel metabolites were characterized by interpretation of spectroscopic data.

The sponge Haliclona lunisimilis from Point Loma, California, contained six known chlorinated acetylenes, previously isolated from the dorid nudibranch Diaulula sandiegensis, and three new metabolites, (1Z,3Z)-1-chlorohexadeca-1,3-diene-5,7-diyne-14-ol, (1Z,3E,9Z)-15-acetoxy-1-chlorohexadeca-5,7-diyne-1,3,9-triene, and (1Z,3E)-14-acetoxy-1-chlorohexadeca-1,3-diene-5,7-diyne. The structures of the new compounds were elucidated by interpretation of spectroscopic data. The relationship between the sponge metabolites and the nudibranch metabolites is discussed.

Four beta-carbolines, plakortamines A-D, two cyclic peroxides, epiplakinic acids G and H, and two related gamma-lactones, (2S,4R)- and (2R,4R)-2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactones, were isolated from the deep-water sponge Plakortis nigra from Palau. The structures of the eight new metabolites were elucidated by interpretation of spectroscopic data. Most of the metabolites inhibited the HCT-116 human colon tumor cell line.

A specimen of the sponge Myriastra clavosa from the Philippines contained five new isotactic polymethoxydienes 1-5 that form a homologous series. The structures of the isotactic polymethoxydienes, which exhibited moderate cytotoxicity, were elucidated by interpretation of spectroscopic data.

As part of a search for novel inhibitors of cathepsin K, the MeOH extract of a Micronesian sponge of the order Haplosclerida was shown to be active. Bioassay-guided fractionation of the extract yielded halitoxins, tryptamine, and a novel tryptamine-derived alkaloid, haploscleridamine (1). The tetrahydro-beta-carboline structure of haploscleridamine (1) was elucidated through spectral techniques. Haploscleridamine (1) was found to be an inhibitor of cathepsin K with an IC(50) of 26 microM.

A specimen of the sponge Myriastra clavosa from the Philippines contained two dimeric macrolides, clavosolides A and B. Clavosolide A is a symmetrical dimer, while clavosolide B is rendered unsymmetrical by the replacement of one of the methoxyl groups by a hydroxyl group. The structures of the clavosolides were elucidated by interpretation of spectroscopic data.

Some halogenated organic compounds, such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polybrominated diphenyl ethers (PBDEs), have been suggested to have natural sources but separating these compounds from their commercially synthesized counterparts is difficult. Molecular-level 14C analysis may be beneficial since most synthetic compounds are manufactured from petrochemicals (14C-free) and natural compounds should have "modern" or "contemporary" 14C levels. As a baseline study, we measured, for the first time, the 14C abundance in commercial PCB and PBDE mixtures, a number of organochlorine pesticides, as well as one natural product 2-(3',5'-dibromo-2'-methoxyphenoxy)-3,5-dibromoanisole. The latter compound was isolated from a marine sponge and is similar in structure to a PBDE. All of the synthetic compounds were 14C-free except for the pesticide toxaphene. which had a modern 14C abundance, as did the brominated natural compound. The result for toxaphene was not surprising since it was commercially synthesized by the chlorination of camphene derived from pine trees. These results suggest that measuring the 14C content of halogenated organic compounds may be quite useful in establishing whether organic compounds encountered in the environment have natural or synthetic origins (or both) provided that any synthetic counterparts derive from petrochemical feedstock.

A new 4-methylene sterol, 7alpha-hydroxytheonellasterol (3), was isolated from the Philippines sponge Theonella swinhoei, along with the known compounds theonellasterol (1) and bistheonellide A. The structure of 3 was elucidated by interpretation of its spectroscopic data, which were compared with those of 1.

A specimen of Plakortis lita from Palau yielded the new carboxylic acids, homo-plakotenin (2a), the sodium salt of homo-plakotenin (2b), the sodium salt of nor-plakotenin (3), the sodium salt of plakotenin (1b), and the known compound plakotenin (1a). The structures of the new acids were elucidated by interpretation of spectral data and by comparison with the known compound. Compounds 1a, 1b, and 2a were found to significantly reduce proliferation of rheumatoid synovial fibroblasts.

Three new cyclic peroxides 5-7 and a new carboxylic acid ester 8 were isolated as minor metabolites from the hexane extract of a Plakinastrella species from the Philippines. The structures of compounds 5-8 were elucidated by interpretation of spectral data and by chemical interconversion, and the absolute stereochemistry of peroxide 6 was determined by application of Mosher's method to a derivative. Although the major compounds in the sponge showed activity against Candida albicans prior to decomposition, the minor metabolites 5-8 are essentially inactive.

A specimen of Dysidea sp. from Palau contained three new dolabellane diterpenes 1-3 and an unstable 14-membered macrolide, arenolide (4), which showed modest cytotoxicity. From a chemotaxonomic viewpoint, these metabolites are so unusual that we discuss their possible origin.

Members of the kinesin superfamily of motor proteins are essential for mitotic and meiotic spindle organization, chromosome segregation, organelle and vesicle transport, and many other processes that require microtubule-based transport. A compound, adociasulfate-2, was isolated from a marine sponge, Haliclona (also known as Adocia) species, that inhibited kinesin activity by targeting its motor domain and mimicking the activity of the microtubule. Thus, the kinesin-microtubule interaction site could be a useful target for small molecule modulators, and adociasulfate-2 should serve as an archetype for specific inhibitors of kinesin functions.

Two novel sesterterpenoids, 12 alpha-acetoxy-19 beta-hydroxyscalara-15,17- dien-20,19-olide (3) and 12 alpha,-16 beta-diacetoxyscalarolbutenolide (5), and a new 9,11-secosterol, 3 beta-hydroxy-5 alpha,6 alpha-epoxy-9-oxo-9,11-seco-5 alpha-cholest-7-en-11-al (6), were isolated from the marine sponge Spongia matamata from Palau together with the known compounds scalarin (1) and 12 alpha-acetoxy-16 beta-hydroxyscalarolbutenolide (4). The structures were determined by interpretation of spectroscopic data.

The Palauan sponge Luffariella sp. contained manoalide (6) and secomanoalide (7) as the major metabolites. The minor metabolites, luffasterols A-C (3-5) are 9,11-secosterols that contain a 3 beta-acetoxy-5 alpha,6 alpha-epoxy-9-oxo-9,11-secocholest-7-en-11-al ring system joined to three different side chains. The structures of the luffasterols were elucidated by interpretation of spectroscopic data.

The marine sponge Theonella swinhoei (lithistid Family Theonellidae, Order Astrophorida) has yielded many important, bioactive natural products, most of which share structural features with bacterial natural products. The presence of microbial symbionts in T. swinhoei has been reported, and it was originally suggested that the cytotoxic macrolide swinholide A and many of the bioactive cyclic peptides from T. swinhoei were all produced by simbiotic cyanobacteria. By transmission electron microscopy, we found four distinct cell populations to be consistently present in T. swinhoei: eukaryotic sponge cells, unicellular heterotrophic bacteria, unicellular cyanobacteria and filamentous heterotrophic bacteria. Purification and chemical analyses of each cell type showed the macrolide swinholide A to be limited to the mixed population of unicellular heterotrophic bacteria, and an anti-fungal cyclic peptide occurred only in the filamentous heterotrophic bacteria. Contrary to prior speculation, no major metabolites were located in the cyanobacteria or sponge cells.

Seven new pyrroloiminoquinone alkaloids, makaluvamines H-M [19-24] and damirone C[25], together with the known compounds, makaluvamines C[13], D[14], and G[17], were isolated from the sponge Zyzzya fuliginosa collected at Nahpali Island, Pohnpei, Micronesia. The structures of the new compounds were elucidated by interpretation of spectral data. The chemotaxonomic relationships involving the makaluvamines and related pyrroloiminoquinone alkaloids are discussed.

The sponge Dysidea fragilis from Pohnpei contained four azacyclopropene derivatives, (4E)-S-dysidazirine [2], which is the optical enantiomer of the known compound dysidazirine [1], (4Z)-dysidazirine [3], (4E)-S-antazirine [4], and (4Z)-antazirine [5]. The structures of the new compounds were elucidated by interpretation of spectral data.

The major metabolite of the Philippine sponge Oceanapia sp. is the antimicrobial alkaloid oceanapamine [1], which was isolated as a trifluoroacetate salt. The structure and the absolute configuration of oceanapamine, which consists of a monocyclic sesquiterpene attached to a histamine residue, were elucidated by interpretation of spectroscopic data.

The Palauan sponge Axinyssa aplysimoides contained (3S*,5R*,6R*,9R*)-3-isocyano-1(10)-cadinene[2],(3S*,5R*,6R*, 9R*)-3-formamido-1(10)-cadinene[3], and (E)-(4-hydroxystyryl)trimethylammonium chloride [6], together with the known diterpenes (-)-neoverrucosan-5beta-ol[4] and (+)-homoverrucosan-5beta-ol[5].

An inseparable two-sponge association, consisting of a Haliclona sp. and a choristid sponge, yielded two unstable enol sulfates, (1E)-2- (3',4'-dihydroxyphenyl)ethylene sulfate [3] and (1Z)-2-(3',4'-dihydroxyphenyl)ethylene sulfate [4]. Methanolysis converted the enol sulfates into 2-(3',4'-dihydroxyphenyl)-1,1,2-trimethoxyethane [5] by an oxidative mechanism.

Six new diterpene isonitriles, 10-epi-isokalihinol F [1], 10-epi-isokalihinol H [2], 1-epi-kalihinene [4], 15-isothiocyanato-1-epi-kalihinene [5], 1,10-diepi-kalihinene [6], and kalihipyran [7] were isolated, together with the known compound isokalihinol B [3], from Acanthella cavernosa collected in the Seychelles. The structures of the new diterpenes were elucidated by interpretation of spectral data. The ring system of kalihipyran [7] differs from that of the kalihinols and kalihinenes.

We have identified a novel natural metabolite, ilimaquinone (IQ), from sea sponges that causes Golgi membranes to break down completely in vivo into small vesicular structures (called vesiculated Golgi membranes [VGMs]). Under these conditions, transport of newly synthesized proteins from endoplasmic reticulum (ER) to the cis-Golgi-derived VGMs is unaffected; however, further transport along the secretory pathway is blocked. Upon removal of the drug, VGMs reassemble rapidly into a Golgi complex, and protein transport is restored. By employing a cell-free system that reconstitutes vesicular transport between successive Golgi cisternae, we provide evidence that the inhibition of protein transport by IQ is specifically due to an inhibition of transport vesicle formation. In addition, like brefeldin A (BFA), IQ treatment prevents the association of beta-COP and ADP-ribosylation factor to the Golgi membranes; however, unlike BFA treatment, there is no retrograde transport of Golgi enzymes into ER.

The Caribbean sponge Plakortis angulospiculatus contains a perlactone, plakinidone, that was identified by interpretation of spectral data. Plakinidone is the first natural product that incorporates a six-membered perlactone ring.

Two antimicrobial fractions were obtained from the sponge Calyx podatypa from the Bahamas. The less polar fraction contained the known compounds xestamines A [1] and B [2] and three new metabolites called xestamines D [3], E [4], and F [5]. The more polar fraction consisted of a mixture of xestamines G [6] and H [7].

Nine diterpenes have been isolated from the marine sponge Chelonaplysilla sp. collected in Pohnpei, Federated States of Micronesia. These include the known diterpenes 1-bromo-8-ketoambliol A acetate, dendrillolide A, dendrillolide D, norrisolide, 12-desacetoxyshahamin C, and aplyviolene. Three novel rearranged spongian diterpenes, chelonaplysins A, B, and C, were identified by interpretation of spectral data and chemical correlation with known compounds. Aplyviolene, chelonaplysin B, and chelonaplysin C exhibited antimicrobial activity against the bacterium Bacillus subtilis. The secondary metabolite composition of this collection of Chelonaplysilla sp. is compared to the composition previously reported for samples from Palau.

Luffolide (4) is a minor metabolite of the sponge Luffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products 5 and 6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A2.